RESUMO
PURPOSE: In patients with COPD, one of the leading indications for domiciliary non-invasive ventilation (NIV), a major paradigm shift has been observed over the past decade in the method for adjusting NIV settings, with the use of sufficient ventilatory support to achieve a significant reduction in PaCO2. Whether this approach may be relevant to other populations, especially slowly progressive neuromuscular diseases (NMD), is unknown. METHODS: This study was conducted as a post hoc analysis from a previously published randomized controlled trial (NCT03458507). Patients with NMD treated with domiciliary NIV were stratified according to the level of ventilatory support: high-level tidal volume (HLVT; mL/kg of predicted body weight [PBW]) or high-level pressure support (HLPS), defined as a value above median value of the whole population (> 6.8 mL/kgPBW or 9.0 cmH2O, respectively). Primary outcome was mean nocturnal transcutaneous CO2 pressure (PtcCO2). Secondary outcomes included adherence to NIV, leaks, and side effects. RESULTS: Of a total of 26 patients, 13 were exposed to HLVT, with significantly lower nocturnal PtcCO2 (respectively 40.5 ± 4.2 vs. 46.3 ± 3.9 mmHg, p = 0.002). A linear correlation between VT (mL/kgPBW) and mean nocturnal PtcCO2 was evidenced (r = - 0.59, 95%CI [- 0.80; - 0.25], p = 0.002). No significant impact of HLVT was found on secondary outcomes. CONCLUSION: Despite the lack of power of this post hoc analysis, our results suggest that higher levels of ventilatory support are correlated with lower PtcCO2 in patients with NMD. Further studies are desirable to assess the extent to which the level of assistance influences PaCO2 evolution in patients with slowly progressive NMD, as well as in restrictive thoracic disorders.
Assuntos
Doenças Neuromusculares , Ventilação não Invasiva , Humanos , Ventilação não Invasiva/métodos , Hipercapnia/terapia , Respiração Artificial , Respiração com Pressão Positiva/métodos , Doenças Neuromusculares/terapia , Doenças Neuromusculares/complicaçõesRESUMO
Electronic cigarettes (e-cigarettes) are becoming the fashionable alternative to decrease tobacco smoking, although their impact on health has not been fully assessed yet. The present study was designed to compare the impact of e-cigarette refill liquid (e-liquid) without nicotine to e-liquid with nicotine on rat testis. For this purpose, e-liquid with nicotine and e-liquid without nicotine (0.5 mg/kg of body weight) were administered to adult male Wistar rats via the intraperitoneally route during four weeks. Results showed that e-liquid with or without nicotine leads to diminished sperm density and viability, such as a decrease in testicular lactate dehydrogenase activity and testosterone level. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis identified a reduction in cytochrome P450 side-chain cleavage (P450 scc) and 17 beta-hydroxysteroid dehydrogenase (17ßHSD) mRNA level, two key enzymes of steroidogenesis. Following e-liquid exposure, histopathological examination showed alterations in testis tissue marked by germ cells desquamation, disorganization of the tubular contents of testis and cell deposits in seminiferous tubules. Finally, analysis of oxidative stress status pointed an outbreak of antioxidant enzyme activities such as superoxide dismutase, catalase and gluthatione-S-transferase, as well as an important increase in sulfhydril group content. Taken together, these results indicate that e-liquid per se induces toxicity in Wistar rat testis, similar to e-liquid with nicotine, by disrupting oxidative balance and steroidogenesis.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/efeitos adversos , Nicotina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Biomarcadores/sangue , Injeções Intraperitoneais , L-Lactato Desidrogenase/sangue , Masculino , Nicotina/administração & dosagem , Ratos Wistar , Contagem de Espermatozoides , Espermatozoides/patologia , Testículo/enzimologia , Testículo/patologia , Testosterona/sangueRESUMO
Airway clearance techniques aim to eliminate excess of bronchopulmonary secretions. Common airway clearance methods involve manual techniques or the use of (oscillatory) positive expiratory pressure systems. In some clinical situations, these techniques may be ineffective, and the physiotherapist will require pneumatic instrumental support. Unfortunately, these devices are expensive and burdensome. Moreover, as their utilization requires specialized expertise, they are seldom used by practitioners. This article describes the pneumatic instrumental supports mainly used in France for airway clearance techniques currently available. We explain their key characteristics, how they function, and their basic settings according to different indications.
Assuntos
Oscilação da Parede Torácica , Fibrose Cística , Oscilação da Parede Torácica/métodos , Humanos , Muco , Modalidades de Fisioterapia , Fenômenos Fisiológicos Respiratórios , Terapia Respiratória/métodosRESUMO
In subjects with neuromuscular diseases (NMD), the choice of facemask is essential for successful long-term noninvasive ventilation (NIV). While nasal masks usually represent the first line of treatment, almost a third of our subjects with NMD use an oro-nasal interface. Factors associated with the choice of mask remain poorly understood. We provide an original analysis of a previous prospective, multi-centric, Franco-Belgian survey investigating the factors associated with the type of nocturnal mask used in 116 adult NMD subjects treated with NIV. In these patients oro-nasal mask use was more often associated with non-Duchenne muscular dystrophy, older subjects, higher body mass index, better upper limb autonomy allowing independent mask removal and shorter periods of ventilation. Controlled prospective studies are needed to compare the efficacy and tolerance of different interfaces in this specific population.
Assuntos
Comportamento de Escolha/fisiologia , Máscaras , Doenças Neuromusculares/terapia , Ventilação não Invasiva/instrumentação , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Insuficiência Respiratória/terapia , Adulto , Fatores Etários , Idade de Início , Índice de Massa Corporal , Desenho de Equipamento , Feminino , Humanos , Masculino , Máscaras/estatística & dados numéricos , Pessoa de Meia-Idade , Doenças Neuromusculares/complicações , Doenças Neuromusculares/epidemiologia , Ventilação não Invasiva/estatística & dados numéricos , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Insuficiência Respiratória/complicações , Insuficiência Respiratória/epidemiologia , Fatores SocioeconômicosRESUMO
OBJECTIVES: To determine, in a population of women with preterm labor and intact membranes, whether ultrasound cervical length measurement performed only in patients selected according to the Bishop score predicts imminent preterm delivery better than does systematic cervical length measurement in the entire population. METHODS: The Bishop score and sonographic cervical length were recorded prospectively in women with preterm labor between 24 and 34 completed weeks' gestation. Outcome measures were preterm delivery within 48 h and within 7 days. Predictive values were calculated for each marker separately and then in combination. RESULTS: Of the study population of 395 women, 17 (4.3%) and 32 (8.1%) delivered within 48 h and within 7 days, respectively, following inclusion. For delivery within 7 days, areas under the Bishop score (0.848) and sonographic cervical length (0.813) receiver-operating characteristics curves did not differ significantly. For the selective use of sonographic cervical length measurement in patients selected according to the Bishop score, the test was considered positive if the Bishop score was >or= 8, or 4-7 with cervical length Assuntos
Parto Obstétrico
, Seleção de Pacientes
, Nascimento Prematuro
, Adulto
, Medida do Comprimento Cervical
, Maturidade Cervical
, Membranas Extraembrionárias
, Feminino
, Humanos
, Funções Verossimilhança
, Trabalho de Parto Prematuro
, Gravidez
, Resultado da Gravidez
, Segundo Trimestre da Gravidez
, Terceiro Trimestre da Gravidez
, Estudos Prospectivos
, Sensibilidade e Especificidade
RESUMO
The phospholipid requirement of the (Ca2+ + Mg2+)-ATPase present in a membrane fraction from human platelets was studied using various purified phospholipases. Only those phospholipases, which hydrolyse the negatively charged phospholipids, inhibited the (Ca2+ + Mg2+)-ATPase activity. The ATPase activity could be restored by adding mixed micelles of Triton X-100 and phosphatidylserine or phosphatidylinositol. Micelles with phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine or sphingomyelin could not be used for reconstitution and inhibited the activity of the native enzyme.
Assuntos
Plaquetas/enzimologia , ATPases Transportadoras de Cálcio/sangue , Fosfolipídeos/sangue , Adenosina Trifosfatases/sangue , ATPase de Ca(2+) e Mg(2+) , Cálcio/farmacologia , Humanos , Fosfolipases/sangue , Fatores de TempoRESUMO
Several nucleotide triphosphates (NTPs) were tested as energy source for the Ca2+ uptake by human platelet membrane vesicles. The Ca2+ uptake by these membranes was driven by ATP, GTP, ITP, UTP and CTP. The steady-state level of accumulated Ca2+ was equal with the different NTPs. The highest uptake velocity was found with ATP, but about 40-80% of the velocity with ATP could be accomplished with the other nucleotides. The highest affinity was also found with ATP (Km apparent = 15 microM). The liberation of Pi from the various NTPs was measured simultaneously with the Ca2+ uptake. The coupling ratio (moles of Ca2+ taken up/moles of Pi liberated) varied from 0.4 for ATP to 2.3 for UTP and was almost independent of the NTP concentration. The enzyme activity with ATP as substrate is strongly dependent on the Ca2+ concentration in contrast to the activity with GTP, ITP, UTP or CTP.
Assuntos
Plaquetas/metabolismo , Cálcio/sangue , Ribonucleotídeos/sangue , Transporte Biológico Ativo , Membrana Celular/metabolismo , Humanos , Hidrólise , Cinética , Relação Estrutura-AtividadeRESUMO
Unstimulated RAW 264.7 macrophages express negligible heme oxygenase-1 (HO-1) protein but incubation with the nitric oxide (NO) donor spermine nonoate (SPNO) induced HO-1 and weakly cyclo-oxygenase-2 (COX-2) protein. This effect was potentiated by coincubation with the COX-2 selective inhibitor, SC58125. Cells incubated with SPNO showed a strong increase in HO-1 mRNA levels after 4 h with a significant potentiation in the presence of SC58125, which did not modify HO-1 mRNA stability. The induction of HO-1 by NO and its potentiation by anti-inflammatory agents may play a role in inflammatory and immune responses.
Assuntos
Heme Oxigenase (Desciclizante)/biossíntese , Macrófagos/efeitos dos fármacos , Óxido Nítrico/farmacologia , Animais , Linhagem Celular , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Sinergismo Farmacológico , Heme Oxigenase-1 , Isoenzimas/antagonistas & inibidores , Isoenzimas/biossíntese , Macrófagos/enzimologia , Proteínas de Membrana , Camundongos , Óxidos de Nitrogênio , Prostaglandina-Endoperóxido Sintases/biossíntese , Pirazóis/farmacologia , RNA Mensageiro/biossíntese , Espermina/análogos & derivados , Regulação para CimaRESUMO
Vascular endothelial cell addressins play an important role in lymphocyte homing in secondary lymphoid organs and in chronic inflammatory areas. A SV40 large T antigen-immortalized cell line from peripheral lymph nodes, HECa1O [Bizouarne et al., 1993a], was used to characterize the location of addressins with regard to environmental factors and cytokines. For this purpose, two monoclonal antibodies, MECA 79 and MECA 367, specific for peripheral lymph node vascular addressin and for mucosal addressin (Peyer's patches), respectively, were bound to unstimulated HECa1O cells. Both mucosal and peripheral addressins were detected inside the cells and in cellular extracts of the resting cells. On the cell surface, both addressins could be evidenced on the same cells at a moderate level of expression. They partly mediate the EL4/EL4IL2 lymphoma cells' adhesion to HECa1O cells. Supernatants of cultured peripheral lymph node or Peyers' patch cells induced expression of MECA 79 or MECA 367 antigens, respectively, on the surface of HECa1O cells. Interleukins, IL-7, IL-3, and IL-8, induced the cell-surface appearance of MECA 79 but not of MECA 367 antigen. Therefore, the same cell type synthesizes both antigens, but the expression of these antigens on the cell surface is independently regulated, thus uncovering a characteristic tissue type-specific as well as environment-sensitive properties of microvascular endothelial cells.
Assuntos
Antígenos de Superfície/metabolismo , Endotélio Vascular/imunologia , Imunoglobulinas/metabolismo , Linfonodos/citologia , Mucoproteínas/metabolismo , Receptores de Retorno de Linfócitos/metabolismo , Animais , Western Blotting , Adesão Celular , Moléculas de Adesão Celular , Células Cultivadas , Citocinas/farmacologia , Citometria de Fluxo , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Peso Molecular , Nódulos Linfáticos Agregados/citologiaRESUMO
The serine protease thrombin present at the site of vascular injury triggers fibrin formation, platelet activation and different cellular responses including angiogenesis. We report a role for thrombin in the human monolayer cultured endothelial cell growth and angiogenesis in 3D collagen gel angiogenesis assay. The angiogenic activity of thrombin is, in part, related to the expression of the vascular endothelial growth factor (VEGF)165 mRNA, assessed by reverse transcriptase-polymerase chain reaction, either in monolayer cultured endothelial cells or in endothelial cells forming capillary-like structures in the 3D collagen gel assay. This expression of VEGF mRNA is associated with a VEGF secretion in the supernatant of thrombin-treated human umbilical vein endothelial cells. The thrombin-induced VEGF165 mRNA expression is associated with the regulation of hypoxia-inducible factor 1alpha, analyzed by Western Blot, in endothelial cells.
Assuntos
Endotélio Vascular/citologia , Neovascularização Fisiológica/efeitos dos fármacos , Trombina/farmacologia , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , RNA Mensageiro/biossíntese , RNA Mensageiro/efeitos dos fármacos , Trombina/fisiologia , Fatores de Transcrição/análise , Fatores de Transcrição/biossíntese , Fatores de Transcrição/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The effect of cAMP (which involved a 23 kDa protein phosphorylation) has been studied on the Ca2+ uptake and Ca2+ release from a human platelet membrane vesicle fraction. It was tested in the presence of the catalytic subunit of the cAMP-dependent protein kinase (C Sub). The addition of C Sub increased the steady state level of the Ca2+ uptake into the membrane vesicles. The effect was enhanced when tested in the absence of Ca2+ precipitating agent. The response was proportional to the dose of C Sub. Moreover, the effect varied with the Ca2+ concentration. The effect of C Sub has been tested on the inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release. A phosphorylated state of the 23 kDa protein appeared to be necessary. Indeed, a phosphorylation inhibition prevented the IP3 effect and the addition of C Sub increased the percentage of released Ca2+ (without modification of the time course). However, the C Sub dose-dependent response was not linear. The effect of cAMP on the two functions (Ca2+ uptake and Ca2+ release) appears to be different. Therefore, these results led us to suggest a more complex role of cAMP in the regulation of platelet Ca2+ concentration.
Assuntos
Plaquetas/metabolismo , Cálcio/sangue , AMP Cíclico/sangue , Catálise , Membrana Celular/metabolismo , AMP Cíclico/fisiologia , Humanos , Inositol 1,4,5-Trifosfato , Fosfatos de Inositol/farmacologia , Fosforilação , Proteínas Quinases/metabolismoRESUMO
Human blood platelets stimulated by thrombin undergo very rapid morphological changes, the most characteristic of which are pseudopod formation and granule centralization. These early changes in shape are accompanied by a transient decrease (30%) in phosphatidyl inositol 4,5-bisphosphate (PIP2) which occurs in the first 10 s after thrombin addition. Transient decreases in phosphatidyl inositol 4-phosphate (PIP) and phosphatidyl inositol (PI) occur later (20-30 s). These events lead to the formation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG) and hence phosphatidate (PA). Two polypeptides are phosphorylated during the same time span: the myosin light chain (P20) and a 43 kDa protein (P43). Concomitant with these molecular changes, platelet 'release reaction' occurs, i.e., liberation of the different granule constituents into the external medium: the earliest concerns dense bodies which liberate adenine nucleotides, calcium and serotonin; alpha-granules then liberate adhesive and specific proteins and are followed by lysosomes which liberate hydrolases. Pathological platelets from patients with inherited disorders, presenting well-characterized and specific defects of either the platelet membrane (GT) or storage granules (GPS and HPS), have also been studied. The results obtained lead to the following conclusions: (1) the transducing system is normal in platelets unable to aggregate; (2) phosphorylation of P20 and P43 proteins can be complete with impaired release; and (3) when platelets lack alpha-granules the transducing system as well as the release of other granule populations are impaired. These results evidence the relationship between the absence of intraplatelet components and metabolic events.
Assuntos
Transtornos Plaquetários/sangue , Plaquetas/fisiologia , Comunicação Celular/efeitos dos fármacos , Trombina/farmacologia , Plaquetas/efeitos dos fármacos , HumanosRESUMO
It was previously shown that Wheat germ agglutinin, (WGA)-induced platelet activation occurred when only 17% of the lectin binding sites were occupied on the platelet surface and WGA caused the release of a platelet constituent which in turn participates in the observed effect. We now further define the platelet activation induced by WGA: the lectin induces a binding of fibrinogen to specific surface receptors. 125I-fibrinogen binding increases with the WGA concentration from 5 to 15 micrograms/ml. Binding occurs without addition of exogenous calcium; its analysis demonstrated 54,000 sites with a Ka = 0.8 X 10(6) M-1. Addition of 1 mM Ca2+ enhances the 125I-fibrinogen binding and reveals a second class of sites with higher affinity (9200 sites, Ka = 0.17 X 10(8) M-1). This 125I-fibrinogen binding is totally abolished by EDTA, ATP and arginine, and inhibited by 75% by CP/CPK; cyclooxygenase inhibitors and PGE1 also reduce the fibrinogen binding. Thus the WGA-induced fibrinogen binding is release-dependent and responsible for the aggregation process but not for the agglutinating effect of the lectin.
Assuntos
Plaquetas/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas/efeitos dos fármacos , Aglutininas do Germe de Trigo/farmacologia , Alprostadil/farmacologia , Arginina/farmacologia , Plaquetas/ultraestrutura , Relação Dose-Resposta a Droga , Ácido Edético/farmacologia , Fibrinogênio/metabolismo , Humanos , Cinética , Agregação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas/fisiologia , Ligação ProteicaRESUMO
We have used the mepacrine-labelling procedure to measure the dense body (serotonin storage organelle) content of the platelets of 2 hereditary disorders where abnormalities in dense body number were suspected. The platelets were incubated with mepacrine and examined by fluorescence microscopy. A mean number of 5.4 +/- 0.8 (SD) dense bodies per platelet was calculated from the data obtained using platelets isolated from 40 normal human subjects. In contrast the platelets of 2 patients with the Bernard-Soulier syndrome contained an average of 14 and 17 labelled granules. This increase was associated with a much greater capacity of the platelets to accumulate 14C-5-HT. The opposite result was obtained using the platelets from 2 patients with the Hermansky-Pudlak syndrome which contained few granules labelled by mepacrine and took up less 14C-5-HT than normal human platelets. Centrifugation of the patients' platelets on discontinuous sucrose gradients showed that the platelets of the 2 Bernard-Soulier patients were much denser than normal whereas a high proportion of low density platelets was observed in the Hermansky-Pudlak syndrome. These results further define the platelet abnormalities in the two syndromes and suggest that dense body number may be one of the factors governing platelet density.
Assuntos
Transtornos Plaquetários/sangue , Plaquetas/metabolismo , Quinacrina/metabolismo , Serotonina/metabolismo , Adolescente , Adulto , Plaquetas/classificação , Radioisótopos de Carbono , Separação Celular , Criança , Grânulos Citoplasmáticos/metabolismo , Feminino , Humanos , Masculino , SíndromeRESUMO
Nitric oxide (NO) regulates cyclo-oxygenase (COX) activity in various cell systems and reports conflict in regard to its stimulatory versus inhibitory role. Incubation of human umbilical vein endothelial cells (HUVEC) with SIN-1 (3-morpholinosydnonimine), a donor of NO, resulted in a rapid and dose-dependent increase in the expression of COX-2 as analysed by Western and Northern blotting. Incubation of HUVEC with SIN-1 and interleukine (IL)-1alpha resulted in increased induction of COX-2 compared with IL-1alpha alone and corresponded to an additive effect. The COX-2 induction was dependent on a de novo synthesis since cycloheximide, an inhibitor of protein synthesis, blocked the enzyme expression. The increase in COX-2 expression was not accompanied by a corresponding change in prostaglandin (PG) production. However, the COX activity was partially recovered when immunoprecipitated COX-2 was incubated with arachidonic acid and haematin. Peroxynitrite, a highly reactive nitrogen molecule derived from the interaction of NO and superoxide anion, significantly increased COX-2 expression. Under these conditions and within the limit of detection of the antibody, selective antibody for nitrotyrosine failed to detect nitrated COX-2 in immunoprecipitated COX-2 when cells where incubated with SIN-1 or SIN-1+IL-1alpha. Ro 31-8220, a specific inhibitor of protein kinase (PK) C, blocked the induction of COX-2. Also, SB203580, the selective inhibitor of p38 MAP kinase, strongly blocked the induction of COX-2 by SIN-1 in the presence or absence of IL-1alpha, whereas the MEK-1 inhibitor, PD 98059, affected it to a lesser extent. These data demonstrate that SIN-1 induces COX-2 in HUVEC in the absence of PG formation and suggest a complex regulation of COX-2 expression and PG formation by NO in endothelial cells.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Isoenzimas/metabolismo , Molsidomina/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/biossíntese , Northern Blotting , Western Blotting , Linhagem Celular , Ciclo-Oxigenase 2 , Relação Dose-Resposta a Droga , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Interleucina-1/farmacologia , Isoenzimas/genética , Proteínas de Membrana , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Molsidomina/análogos & derivados , Nitratos/farmacologia , Testes de Precipitina , Prostaglandina-Endoperóxido Sintases/genética , Piridinas/farmacologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
1. Haem oxygenase-1 (HO-1) can exert protective effects against oxidative stress and inflammation. Fibroblasts participate in inflammatory responses where they produce high levels of prostaglandins (PGs) and nitric oxide (NO). However, little is known of the presence of HO-1 in these cells and the possible interactions among these pathways. Incubation of cells with NO donors, spermine nonoate (SPNO) and S-nitroso-N-acetylpenicillamine (SNAP), induced a dose- and time-dependent expression of HO-1 protein. 2. NO donors increased basal PGE(2) release although they reduced PGE(2) accumulated in the medium and cyclo-oxygenase (COX) activity when cells were stimulated with lipopolysaccharide (LPS). COX-2 protein was weakly induced by SPNO in basal conditions and in the presence of LPS a synergy for HO-1 and COX-2 protein expression was observed. 3. Our results indicate that reactive oxygen species participate in the inductive effect of NO donors or LPS on HO-1 expression, whereas endogenous NO production may play a role in the mechanism of the synergy exhibited by SPNO and LPS on HO-1 and COX-2 expression. In this system, zinc protoporphyrin IX did not affect nitrite levels but reduced COX activity. 4. The selective COX-2 inhibitors SC58125 and NS398 as well as the non-selective COX inhibitor, indomethacin, strongly reduced PGE(2) synthesis and showed a synergy with NO donors in HO-1 and COX-2 induction. Addition of PGE(2) had no effect, suggesting a mechanism independent of PGs formation. 5. In inflammatory conditions a number of factors could cooperate to induce HO-1 and COX-2, with a positive regulation by COX inhibitors.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios/farmacologia , Dinoprostona/metabolismo , Heme Oxigenase (Desciclizante)/efeitos dos fármacos , Isoenzimas/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Prostaglandina-Endoperóxido Sintases/efeitos dos fármacos , Células 3T3/efeitos dos fármacos , Células 3T3/metabolismo , Animais , Ciclo-Oxigenase 2 , Indução Enzimática , Heme Oxigenase (Desciclizante)/metabolismo , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Isoenzimas/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandina-Endoperóxido Sintases/farmacologiaRESUMO
Binding of wheat germ agglutinin (WGA) to human platelets and their activation were studied. The binding of fluoresceinyl-substituted WGA (F-WGA) was saturable, specific, reversible and cooperative. The apparent association constant (Ka) was 2.4 X 10(6) M-1. Activation of platelets was measured by change in light transmission (LT) (aggregation) and by assays of 14C-serotonin and beta-thromboglobulin (secretion). The maximum platelet activation was obtained with 15 micrograms/ml WGA. At this concentration only 17% of all available binding sites were occupied. Increasing the WGA concentration diminished the change in LT and the secretion from alpha granules but not from dense bodies. The addition of EDTA partially reduced the platelet aggregation without any effect on the secretion. Remaining LT change was insensitive to all metabolic inhibitors tested (CP/CPK, arginine, indomethacin, PGE1, chlorpromazine, colchicine and cytochalasin B). The secretion measured in the presence of EDTA was only reduced by preincubation with PGE1 and CPZ. Succinyl-WGA which only binds glucoconjugates containing GlcNAc did not induce any platelet activation, whereas limulin, which binds to glucoconjugates containing NeuAc did induce platelet agglutination and secretion. These results indicate that: (1) the platelet aggregation and secretion induced by WGA occur with only partial occupancy of the membrane binding sites by the lectin; (2) the platelet LT change is due in part to the agglutinating properties of the lectin bound to the platelet surface, and in another part to the aggregation reaction mediated by a platelet constituent secreted from the storage sites in response to the binding of the lectin.
Assuntos
Plaquetas/metabolismo , Lectinas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Alprostadil , Arginina/farmacologia , Plaquetas/efeitos dos fármacos , Clorpromazina/farmacologia , Colchicina/farmacologia , Creatina Quinase/farmacologia , Citocalasina B/farmacologia , Ácido Edético/farmacologia , Humanos , Técnicas In Vitro , Indometacina/farmacologia , Fosfocreatina/farmacologia , Prostaglandinas E/farmacologia , Aglutininas do Germe de TrigoRESUMO
The antenatal diagnosis of a tumour of the heart after 32 weeks of amenorrhoea made us think Bourneville's tuberous sclerosis. This is a familial condition that had not been noted before and which was confirmed after the birth. The diagnosis and prognostic problems that arise when such tumours are discovered in the heart are considered.
Assuntos
Neoplasias Cardíacas/diagnóstico , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Esclerose Tuberosa/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , GravidezRESUMO
Platelet activation induced by NaF or fluoroaluminate (AlF4-) was studied. The latter has been described to substitute for the gamma-phosphate group of the GTP molecule. With 10 mM-NaF, a concentration unable to induce any measurable Ca2+ mobilization (as measured with Indo 1), addition of AlCl3 potentiated platelet aggregation, thromboxane synthesis, diacylglycerol formation and p43 phosphorylation, without any increase in intracellular Ca2+. Neither phosphoinositide hydrolysis nor phosphatidic acid formation could be detected. AlF4- induced the release through a granule centralization within a microtubule bundle, although no myosin light-chain phosphorylation could be detected. Addition of flurbiprofen (10 microM) resulted in only partial inhibition of diacylglycerol formation, with no effect on the release reaction or on p43 phosphorylation. The present results suggest that AlF4- does not stimulate a G-protein governing the phosphoinositide-specific phospholipase C. The AlF4(-)-induced diacylglycerol formation is discussed. Moreover, these results bring evidence that there is no correlation between granule centralization and myosin light-chain phosphorylation.